Cease Report Adv Res Gastroentero Hepatol Volume 2 Issue 4 - January 2017 DOI: 10.19080/ARGH.2017.04.555592 Copyright © All rights are reserved by Deepankar Kumar Basak Heyde’s syndrome: Rarely heard and often missed

Deepankar Kumar Basak1*, Richmond Ronald Gomes2 and Md Samsul Arfin3 1Specialist-, Square Hospitals Ltd., Bhangladesh 2Assistant Professor, Internal , Ad-din Sakina Medical College & Hospital, Bhangladesh 3Gasroenterology, Square Hospitals Limited., Bhangladesh Submission: November 11, 2016; Published: January 19, 2017 *Corresponding author: Deepankar Kumar Basak, MBBS, FCPS (Medicine), Specialist-Gastroenterology, Square Hospital Ltd., Dhaka, Bangladesh, Tel: Email:

Abstract from the is very common and important problem in clinical practice. There are lots of causes of GI bleeding,

gastrointestinal bleeding in an elderly female patient who is also suffering from HCV related decompensated CLD with multiple myeloma. Heyde’sbut sometimes syndrome it is is very now difficultknown to be locate gastrointestinal and treat gastrointestinal bleeding from bleeding. angiodysplasic Here welesions discuss due Heyde’s to acquired syndrome, vWD-2A an secondary important to cause aortic of

stenosis, and the diagnosis is made by confirming the presence of those three things. For this, a wide range of investigations and treatment showingmodalities gastrointestinal are now available. bleeding One aftershould aortic therefore valve makereplacement. an aggressive Old age attempt and co-morbidities to localize the may bleeding create site.a hindrance Newer endoscopic in valve replacement technologies or resectionmay prove . beneficial. Some Aortic newer valve treatment replacement options is claimed like hormonal to minimize and orthalidomide even stop thetherapy bleeding look in promising such patients. but they But stillhave there inadequate are a few evidence reports behind them. Here, we discuss this clinical problem, strategies and evidence, areas of uncertainty, available guidelines, and our conclusions about Heyde’s syndrome.

Keywords: Heyde’s syndrome; gastrointestinal ; Gastrointestinal bleeding

Introduction transfusions. We describe a case of Heyde’s syndrome with is the most common vascular lesion of the multiple angiodysplastic lesions throughout the colon, mostly at gastrointestinal tract, and this condition may be asymptomatic, the distal part and discuss the various challenges in the diagnosis or it may cause gastrointestinal (GI) bleeding [1]. The vessel and treatment of such patients. walls are thin, with little or no smooth muscle, and the vessels are ectatic and thin. It is a degenerative lesion of previously Case Report healthy blood vessels found most commonly in the and Mrs. Chaina Chakraborty, 71 year old pleasant lady, known proximal but bleeding from proximal intestinal to have multiple myeloma (MULTIPLE MYELOMA-IgG Kappa angiodysplasias, and nasal bleeding is also reported [2,3]. After Myeloma and Beta2 Microglobulin-4.2) chronic , it is the second leading cause of lower GI bleeding (HCV related) with (grade 2), duodenal in patients older than 60 years. An association between colonic ulcer and with IHD was admitted to SHL angiodysplasia and aortic stenosis was described by Edward C gastroenterology department through ER with the complaints Heyde et al. [4]. It is caused by the induction of type IIA (vWD-2A) by a depletion of Von Willebrand weakness for same duration. She had previous history of of passage of black tarry stool for last five days and generalized hospital admission for several times in the last three months stenosis. The existence of this syndrome was debated for a factor (vWF) in blood flowing through the narrowed valvular with these same complaints and received 8-10 units of blood and blood products over that period. Now her hemoglobin 5 gastrointestinal bleeding did actually resolve after aortic valve considerable period of time when finally it was shown that the gm/dl, Haematocrit 20.9%, TC 10.5 K/uL, Platelets 40K/uL,

PT, aPTT was normal. Echocardiogram shows narrow LVOT credence to the existence of this syndrome [2,5]. The bleeding replacement in many such patients, thereby giving a definite with Dynamic subvalvular Aortic Stenosis Gr 78/28mmHg could be severe and the patient usually requires multiple blood

Adv Res Gastroentero Hepatol 2(4): ARGH.MS.ID.555592 (2017) 0071 Advanced Research in Gastroenterology & with no AR. shows grade 2 esophageal varix but no We do argon plasma (APC) of angiodysplastic active bleeding from varix. shows angiodysplastic lesion in colon as far as possible in 2 sessions with injection of lesions through the colon with hamorrhoids.Bleeding occur . In this measure she was recovered well and there was most probably from angiodysplastic lesions but we don’t see any no bleeding at least 1 year follow-up. After that again melaena active bleeding from any angiodysplasia. Initially patient was started on/off. She was also treated by desmopressin nasal also platelet aphaeresis (Figure 1). measure decreases her incidence of melaena. We offer her to do managed with with fresh frozen plasma and spray with cap.danazol to increase vWF with inj octreotide. This aortic valvae replacement for further management but she was not interested. Discussion Angiodysplasia is the most common vascular lesion of the gastrointestinal tract, and this condition may be asymptomatic, or it may cause gastrointestinal (GI) bleeding [1]. Seventy- Figure 1: Angioplastic lesion in colon. seven percent of angiodysplasias are located in the cecum and ascending colon, 15% are located in the and , and Our patient is an elderly lady with multiple co-morbidities. the remainder is distributed throughout the alimentary tract. She was treated by thalidomide for multiple myeloma that Nasal bleeding is also reported [2,3]. These lesions typically are was controlled. Two times EVL was done for HCV related nonpalpable and small (< 5 mm). Angiodysplasia may account decompensated CLD with feature of hypersplenism with low for approximately 6% of cases of lower GI bleeding. It may be platelet count. Her past history of multiple episodes of life- observed incidentally at colonoscopy in as many as 0.8% of threatening blood loss makes it necessary to do something to patients older than 50 years. The prevalence for upper GI lesions prevent gastrointestinal blood loss. The options available are is approximately 1-2%.Clinical presentation in patients with angiographic intervention, endoscopic intervention, intestinal resection, aortic valve replacement, and estrogen-progesterone therapy/thalidomide therapy. The patient herself along with angiodysplasia is usually characterized by maroon-colored stool, can be massive in approximately 15% of patients. In 20-25% of her relatives were unwilling for any major surgical intervention , or . Bleeding is usually low grade, but it due to her advanced age and the multiple comorbidities that she and stools that are intermittently positive for occult had, further compromising the likely outcome after the surgery. bleeding episodes, only tarry stools are passed. Iron deficiency blood can be the only manifestations of angiodysplasia in 10- There was a high chance of more angiodysplastic lesion in small 15% of patients. Bleeding stops spontaneously in greater than gut which is not approachable on colonoscopy and there was no 90% of cases but is often recurrent. An association between capsule endoscope in our country. colonic angiodysplasia and aortic stenosis was described by Angiographic intervention is also not preferable as there is Edward C Heyde et al. [4]. a possibility of existence of multiple unnoticed angiodysplasias, The exact mechanism of development of angiodysplasia possibility of gut infarction after angiography, and the deranged is not known, but chronic venous obstruction may play a role renal function of the patient would be a contraindication for [6,7]. Increased expression of angiogenic factors, like basic best and acceptable solution for this patient like aortic valve angiography. All these problems make it difficult to choose the factor (VEGF), is also believed to play a role in the pathogenesis replacement (Figure 2&3). fibroblast growth factor (bFGF) and vascular endothelial growth of colonic angiodysplasia [8]. In Heyde’s syndrome; it seems that bleeding occurs from pre-existing angiodysplasias in the gut. This bleeding is due to an acquired haematological defect caused by aortic stenosis [5,9]. Age-related senile tissue changes may predispose to angiodysplasia and the link between the angiodysplasia and aortic stenosis is controversial [10-12]. Various studies have described the acquired von Willebrand Figure 2: (APC). factor deficiency as being a reason for bleeding in Heyde’s syndrome [5,13]. The haematological defect is identified as Willebrand factor (vWF) [14]. The high shearing force caused deficiency of high molecular weight (HMW) multimers of von by blood jet in aortic stenosis uncoils the HMW multimers of vWF exposing the vWF cleavage site for ADAMST [13]. This leads to selective loss of HMW multimers of vWF due to increased

Figure 3: EVL. Willebrand syndrome type 2A). There is an evidence showing proteolysis. Acquired vWF deficiency state is thus created (von

How to cite this article: Deepankar K B, Richmond R G, Md Samsul A. Heyde’s syndrome: Rarely heard and often missed. Adv Res Gastroentero Hepatol 0072 2017; 2(4): 555592. DOI: 10.19080/ARGH.2017.02.555592 Advanced Research in Gastroenterology & Hepatology normalisation of HMW multimers of VWF after aortic valve performed [20]. Submucosal injection of a saline epinephrine replacement surgery [15-18]. Heydes syndrome consists of a solution followed by the application of APC has been reported [21] New endoscopic techniques such as the Olympus EVIS due to bleeding angiodysplasia or idiopathic bleeding [19]. LUCERA variable indices of hemoglobin chart function have been triad of aortic stenosis, acquired vWF deficiency and anaemia The main challenge is localisation of bleeding source in these developed to assess completeness of vascular mucosal ablation patients [17]. The bleeding source could be hidden and out of reach for conventional .Wireless is central to the management of patients with lower GI bleeding, [22]. Super selective embolization of visceral arterial branches is a useful invention that helps us to visualise the . including bleeding from colonic angiodysplasia [23] Partial or It also guides us about the route for enteroscope insertion. It complete gastrectomy for management of gastric angiodysplasia is a painless and noninvasive procedure. The disadvantages of has been reported to be followed by bleeding in as many as 50% capsule endoscopy include the inability to detect all the lesions, of patients. Rebleeding was attributed to other angiodysplastic especially in presence of active bleeding, and the inability lesions.Right hemicolectomy for angiodysplasia is second- to intervene [17,19]. The double balloon and single balloon line therapy after endoscopic ablation, if repeated endoscopic endoscopies are described to be useful to overcome these coagulation has failed, if endoscopic therapies are not available, disadvantages of capsule endoscopy [14,15]. It is claimed that and for life-threatening hemorrhage. double balloon and single balloon endoscopies can visualise The mortality rate associated with surgical resection ranges most of the small bowel and thus enable diagnostic manoeuvres from 10% to 50%. This is based on the view that surgery carries and therapeutic techniques like achieving haemostasis, a much higher risk in elderly patients, who often have multiple performing polypectomies, stricture dilatation, and stenting. coexisting medical problems, including coronary artery disease, This technique produces superior quality images than capsule coagulopathy, and renal and pulmonary dysfunction. In a study endoscopy. However, the cost and availability of these techniques by Meyer et al, right hemicolectomy resulted in 63% of the could limit their use in developing countries. Therapeutic subjects remaining free of intestinal bleeding (mean follow-up, options for Heyde’s syndrome include aortic valve replacement, 3.6 y), and 37% had some degree of recurrent bleeding [24]. surgery, angiographic intervention, double or single balloon endoscopy,Argon plasma coagulation(APC) and medical therapy The Heyde’s syndrome is supposed to be one of the acquired including hormonal and thalidomide therapy, octreotide [5,19]. It is claimed that aortic valve replacement reduces or even stops guidelines for the diagnosis and management involve detection deficiency states. The recommended gastrointestinal blood loss5. Cessation of bleeding after aortic of vW factor levels, detection of antibodies against the same, valve replacement was found to be associated with improved and treatment with desmopressin or factor viii/vWF. These diagnostic modalities are not readily available across our country and are costly, e.g., in Bangladesh, assessment of vW levels of HMW multimers of vWF after replacement. This finding Heyde’s syndrome. However, advanced age and co-morbidities factor levels may cost more than hormonal therapy for a month. strengthened the hypothesis of acquired vWF deficiency in can make this an unsuitable choice in some patients. A few case There are no recommended guidelines for the management reports describe massive gastrointestinal bleeding after aortic and treatment of Heyde’s syndrome. One should seek help from valve replacement [16]. guidelines for management of occult gastrointestinal blood loss. Also, there should be a consideration for cardiovascular issues Thus aortic valve replacement might not be the ideal and haematological issues of the patient. Various treatment treatment in every patient of Heyde’s syndrome. Surgery and options are available for Heyde’s syndrome but most of them endoscopic therapy especially argon plasma coagulation are not have inadequate evidence behind them. As of now, there is useful in patients with diffuse angiodysplasia. Aortic stenosis and associated cardiac diseases often make patients of Heyde‘s Recurrence of acute hemorrhage from GI angiodysplasia after no universally accepted unified treatment protocol available. hospital discharge occurred in 30% of patients after a mean is mentioned to be able to visualise the small intestine and syndrome unfit for surgery. Though double balloon endoscopy follow-up (33±40 mo). In a multivariate analysis, earlier history intervene, their cost and availability may limit their use. of bleeding with a high bleeding rate, over anticoagulation, Angiographic intervention like embolisation of A-V malformation and the presence of multiple lesions were predictive factors of recurrence. Surprisingly endoscopic APC therapy was not locate and embolise all the lesions in diffuse angiodysplasias. can lead to arterial occlusion and gangrene. It is also difficult to associated with lower rates of recurrent bleeding [25]. A few case reports, one uncontrolled trial, and recently a small double-blind, placebo-controlled, cross-over trial indicate Conclusions and Recommendations that oestrogen-progesterone therapy may be effective in Potentially life-threatening nature, age and co-morbidities, controlling severe recurrent bleeding from gastrointestinal and poorly understood pathophysiology make Heyde’s vascular malformations [17]. Octreotide and estroprogestative syndrome a tough illness to treat. High index of suspicion treatments are the best evaluated drugs; however, no appropriate should be kept in mind while treating aortic stenosis and comparison on cost-effectiveness and tolerance has been gastrointestinal hemorrhage in elderly patients.Involvement

How to cite this article: Deepankar K B, Richmond R G, Md Samsul A. Heyde’s syndrome: Rarely heard and often missed. Adv Res Gastroentero Hepatol 0073 2017; 2(4): 555592. DOI: 10.19080/ARGH.2017.02.555592 Advanced Research in Gastroenterology & Hepatology

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How to cite this article: Deepankar K B, Richmond R G, Md Samsul A. Heyde’s syndrome: Rarely heard and often missed. Adv Res Gastroentero Hepatol 0074 2017; 2(4): 555592. DOI: 10.19080/ARGH.2017.02.555592